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The Effect of Chlorpromazine and Oxypertine on Brain Serotonin and Acetylcholine Levels in the Rat

出版	School of Pharmacy. University of Missouri--Kansas City, 1968
URL	http://books.google.com.hk/books?id=MtLVtgAACAAJ&hl=&source=gbs_api

註釋For several years both serotonin and acetylcholine have been postulated as transmitters or modulators in the central nervous system. Many drugs causing excitation or depression in the CNS have been found to cause changes in the brain levels of acetylcholine or serotonin or both. The purpose of this study is to determine the effects of two tranquilizers, chlorpromazine and oxypertine, on the brain levels of serotonin and acetylcholine and to determine if there is a relationship between changes in these levels and the degree of depression caused by these drugs. Spontaneous motor activity will be hth parameter used to determine the degree of depression caused by these drugs. Male Sprague Dowley rats, 250-35- grams, were separated into groups of six. The test drugs, chlorpromazine and oxypertine were administered I.P., 5 mg/kg. each. One hour following drug administration, spontaneous motor activity was determined for the two drug treated groups and groups of control animals for a twenty minute test period. Spontaneous motor activity was determined for the entire twenty minute period, the initial five minutes, and the terminal five minutes. Immediately following this, the animals were sacrificed, and the brains were assayed for acetylcholine and total and bound serotonin. The results of this study showed an increase in the free/bound serotonin ratio with both drugs, 15.43% with chlorpormazine, and 24.64% with oxypertine. Brain acetylcholine levels were increased with both drugs, with chlorpromazine showing a 25.96% increase and oxypertine showing a 44.6% increase over the control values. These changes in the brain levels of acetylcholine and the free/bound serotonin ratio corresponded roughly with the degree of depression, as determined by spontaneous motor activity studies. Oxypertine caused the greater decrease in spontaneous motor activity at the three time intervals that were tested and showed the greatest change in free/bound serotonin ratio and brain acetylcholine levels. These results indicate that there seems to be a relationship between the increase in the free/bound serotonin ratio and the increase in acetylcholine levels produced by these drugs. While the changes caused by chlorpromazine did not have a high level of significance, the changes caused by oxypertine were significant. The results indicate the oxypertine's tranquilizer activity may be due to changes in the brain sereotonin and acetylcholine levels. These changes in brain levels correlated with the decrease in spontaneous motor activity caused by these two drugs. A possible explanation of these changes may be found in Aprison's theory that serotonin modulates acetylcholine activity in the trophotropic division of the CNS. This proposed mechanism may be involved in the action of oxypertine.